ArticleCellular and molecular gastroenterology and hepatology2020
Tight Junction Protein Claudin-7 Is Essential for Intestinal Epithelial Stem Cell Self-Renewal and Differentiation.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 66 citations in OpenAlex.
- Phosphoproteomic Insights into TRPV4-AMPK Signaling Axis and Barrier Regulation in the Choroid Plexus Epithelium.International journal of molecular sciences · 2026Article
- CLDN7: Epithelial gatekeeper from physiology to pathology‑roles in cancer and epithelial‑related diseases (Review).International journal of molecular medicine · 2026Review
- Claudin proteins as emerging therapeutic targets for solid tumours.Nature reviews. Cancer · 2026Review
- Article
- Intranasal Vaccine Adjuvants and Delivery Platforms: From Barrier Mechanisms to Clinical Translation.Vaccines · 2026Review
- Roles of Tight Junction Proteins in Intestinal Barrier Function and Health of Weaned Piglets: A Review.Veterinary sciences · 2026Review
- Claudins in ovarian cancer: emerging biomarkers and therapeutic targets.Tissue barriers · 2026Review
- Folic acid improves intestinal function in grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Human gut commensalGut microbes · 2025Article
- Claudin Proteins: Their Potential Role in Obesity and Adipose Tissue Signaling, Physiology and Disease.Nutrients · 2025Review
- ACSS2-Mediated Histone H4 Lysine 12 Crotonylation (H4K12cr) Alleviates Colitis via Enhancing Transcription of CLDN7.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Maternal oral sodium propionate supplementation restores gut integrity and mitigates stress-induced metabolic and behavioral outcomes in offspring.Translational psychiatry · 2025Article
- Tannic Acid and Ethacridine Lactate Attenuate Markers of Stress-Induced Intestinal Barrier Dysfunctions in Murine Small Intestinal Organoids.Biomolecules · 2025Article
- Acute enhanced liquid aspirin administration improves performance and intestinal function in nursery pigs.Journal of animal science · 2025Article
- IntratumorCurrent research in microbial sciences · 2025Article
- Review
- Colonic crypt stem cell functions are controlled by tight junction protein claudin-7 through Notch/Hippo signaling.Annals of the New York Academy of Sciences · 2024Article
- Claudin-7 is essential for the maintenance of colonic stem cell homoeostasis via the modulation of Wnt/Notch signalling.Cell death & disease · 2024Article
- Low-Dose Trypsin Accelerates Wound HealingACS pharmacology & translational science · 2024Article
- AnFrontiers in immunology · 2024Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsClaudin-7 (Cldn7) is a tight junction (TJ) membrane protein located at the apical TJ and basolateral side of intestinal epithelial cells. Deletion of Cldn7 by gene targeting leads to the inflammatory bowel disease-like phenotype in mice, which includes weight loss, diarrhea, mucosa ulceration, and severe intestinal epithelial damage. In this study, we test our hypothesis that Cldn7 plays a critical role in regulating intestinal crypt stem cell functions.
methodsGene expression microarray, quantitative reverse-transcription polymerase chain reaction, in situ hybridization, histologic examinations, immunoblotting, 3-dimensional organoid culture, and various treatments to rescue Cldn7-deficient organoid defects were conducted using global Cldn7 knockout mice and inducible, conditional Cldn7 knockout mice.
resultsGene deletion of Cldn7 in intestines showed significant alteration of expression profiles with striking down-regulation of intestinal crypt stem cell markers such as Olfm4, dislocated proliferative cells, and disrupted epithelial cell differentiation. In addition, the isolated Cldn7-deficient crypts where the stem cells reside were either unable to survive at all or formed defective spheroids, highlighting the functional impairment of crypt stem cells in the absence of Cldn7. Remarkably, the Cldn7-expressing organoids with buddings underwent rapid cell degeneration within days after turning off Cldn7 expression in the culture. We identified that activation of Wnt/β-catenin signaling rescued the organoid defects caused by Cldn7 deletion.
conclusionsIn this study, we show that Cldn7 is indispensable in controlling Wnt/β-catenin signaling-dependent intestinal epithelial stem cell survival, self-renewal, and cell differentiation. This study could open a door to study roles of TJ proteins in stem cell regulations in other tissues and organs.
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